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Chronic kidney disease (CKD) is a complex disease caused by both genetic and non-genetic factors, but little is known about the role of their interplay in incident CKD. This study aimed to evaluate associations of a combination of non-genetic factors related to lifestyle, socio-economics, and environment with incident CKD and whether genetic factors influence these associations.
UK biobank (UKB) prospective cohort included 502,369 participants recruited from across the England, Wales, and Scotland in 2006-2010. Participants free of CKD within 3 months after recruitment were included in the study. Follow-up ended when the first episode of CKD, death, or loss of follow-up occurred, or on the censor dates defined by the UKB. A suite of 27 non-genetic explanatory factors falling into four groups—lifestyle, socio-economics, environment and other (e.g., variables related to social support and physical measures) were assessed (Table 1). Polygenic risk score (PRS) for creatinine-based glomerular filtration rate was used to represent the genetic risk for CKD. We first used random survival forests (RSF) to rank the importance of 27 non-genetic explanatory factors in incident CKD. Cox proportional hazards models were then fitted to quantify the associations of PRS, top ten explanatory factors identified by RSF, as well as their interactions with incident CKD.
During a median follow-up of 13.6 years, 17,689 (3.75%) incident CKD cases were reported in 471,738 participants. The risk of incident CKD was more associated with lifestyle, followed by socio-economic and environmental factors (Figure 1). Top ten non-genetic explanatory factors for CKD included current employment status, sleep duration, body mass index (BMI), daily time on TV/computer, daily tea intake, qualifications, daily coffee intake, household income, PM10 pollution, and night shift work. The risk of incident CKD was 1.96-fold higher in those at highest genetic risk compared with those at lowest genetic risk (hazard ratio: 1.96, 95% confidence interval: 1.80-2.13). There was an additive effect for genetic risk and top ten non-genetic explanatory factors on incident CKD risk. Highest risk of incident CKD was observed in participants with highest genetic risk and an unfavorable lifestyle (abnormal sleep duration, long time spent on TV/computer, too much/little tea and coffee intake), socio-economic status (unemployed status, low level of education and family income), environment (high PM10 pollution), and physical measures (high BMI, Figure 2). No multiplicative interactions were identified between these non-genetic explanatory factors and genetic factor for the risk of incident CKD.
This study supports genetic and non-genetic factors were independently associated with incident CKD. These results suggested maintaining a favorable lifestyle/socio-economic status can attenuate the effect of genetics on the risk of CKD.